Salt intake causes B-type natriuretic peptide elevation independently of blood pressure elevation in the general population without hypertension and heart disease

Excessive salt intake causes hypertension and cardiovascular diseases (CVDs). B-type natriuretic peptide (BNP) is synthesized and released from the ventricle, and is a surrogate marker reflecting various CVDs. Moreover, when a slight BNP elevation is shown, it leads to a poor prognosis in the general population. However, the relationship between salt intake and BNP levels in the general population remains unclear, especially in those without hypertension and heart diseases.In this study, we recruited 1404 participants without hypertension and electrocardiogram abnormalities, who received regular annual health check-ups in Japan. Plasma BNP levels were measured, and daily salt intake levels were evaluated using urinary samples. In addition, some clinical parameters were obtained, and the data were cross-sectionally analyzed.The median of plasma BNP levels was 10.50 pg/mL, and daily salt intake was 8.50 ± 1.85 g. When dividing participants into quartiles according to daily salt intake, those with the highest daily salt intake revealed the highest plasma BNP levels. Plasma BNP levels were significantly and positively associated with daily salt intake. Moreover, multiple linear regression analyses revealed that plasma BNP levels showed a significant positive association with daily salt intake levels after adjustments.Plasma BNP levels were significantly and positively associated with daily salt intake after adjustment in the general population. Plasma BNP levels may be a surrogate marker reflecting salt-induced heart diseases.     

Afferent and efferent connections of the nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto‐prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh‐l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello‐prethalamic fibers cross the midline twice to innervate the PTh‐l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon.     

Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration

Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little is known about the intracellular signaling pathway of SCF/KIT-mediated cell migration. To investigate the signaling cascade, we made a series of 22 KIT mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca(2+) mobilization compared to WT. In Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration, and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719-mediated PI3K pathway in cell migration. Combination of Csk and the PI3K inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and the other is Y719-PI3K-Ca(2+) influx.     

Simulation analysis of three intubating supraglottic devices during infant chest compression

Current guidelines for pediatric cardiopulmonary resuscitation suggest that supraglottic devices are alternatives for tracheal intubation with minimal interruption of chest compression. We examined the utility of three intubating supraglottic devices, air‐Q® (air‐Q), Ambu® aura‐i (aura‐i), and i‐gel® (i‐gel), utilizing manikin simulation. Twenty‐two novice physicians performed securing of airway on an infant manikin with the three devices. We measured the rate of success on ventilation and the insertion time with or without chest compression. Successful ventilation rate did not significantly decrease with chest compression in the three devices (without chest compression: air‐Q, 21/22; aura‐i, 20/22; i‐gel, 20/22, during chest compression: air‐Q, 20/22; aura‐i, 20/22; i‐gel, 18/22). The insertion time with air‐Q and aura‐i did not extend significantly for chest compression. In contrast, the insertion time with i‐gel was significantly extended in chest compression (P < 0.05). Air‐Q and aura‐i are more useful for airway management during chest compression than i‐gel.